Group I PAKs in myelin formation and repair of the central nervous system: what, when, and how.

p21-activated kinases (PAKs) are a family of cell division control protein 42/ras-related C3 botulinum toxin substrate 1 (Cdc42/Rac1)-activated serine/threonine kinases. Group I PAKs (PAK1-3) have distinct activation mechanisms from group II PAKs (PAK4-6) and are the focus of this review. In transformed cancer cells, PAKs regulate a variety of cellular processes and molecular pathways which are also important for myelin formation and repair in the central nervous system (CNS). De novo mutations in group I PAKs are frequently seen in children with neurodevelopmental defects and white matter anomalies. Group I PAKs regulate virtually every aspect of neuronal development and function. Yet their functions in CNS myelination and remyelination remain incompletely defined. Herein, we highlight the current understanding of PAKs in regulating cellular and molecular pathways and discuss the status of PAK-regulated pathways in oligodendrocyte development. We point out outstanding questions and future directions in the research field of group I PAKs and oligodendrocyte development.